Existing studies suggest that, while the overall prevalence rates of dementia in Japan and the U.S. are similar, the relative prevalence of Alzheimer's disease (AD) to vascular dementia (VaD) is much greater in the U.S. It is not known whether these differences result from differing study methods or whether they reflect underlying differences in the incidence of dementia subtypes in the two countries with concomitant differences in genetic susceptibility and/or exposure to environmental risk factors. Results from a prevalence survey of a total population of Japanese-Americans aged 65 and over living in King County, WA show that prevalence rates more closely resemble those of Caucasian populations than native Japanese. We propose to (1) follow this cohort over the next five years to (2) determine age- and sex-specific incidence rates of dementia and its subtypes; (3) follow existing prevalent and developing incident cases to monitor the clinical and neuropsychological progression and describe survival in AD and VaD cases, (4) conduct prospective risk factor analyses, including survival analyses, of genetic (apolipoprotein E and family history) and environmental factors for AD and VaD, particularly those affected by lifestyle and diet, and examine potential interactions between genes and environment on the risk of dementia and its subtypes; (5) compare prevalence, incidence as well as relative and attributable risks with methodologically standardized studies in Honolulu, Hiroshima and Machida City. The baseline examination (1992- 1994) contained nearly 2,000 individuals; to cohort of cognitively intact persons contains approximately 1,650. The cognitively intact cohort will be screened every two years, the persons with cognitive impairment are followed annually. Pending the results of an analysis of our screening strategy during the currently funded grant period, we plan to screen the cognitively intact cohort every two years using a cutoff score of 81/100 on the Cognitive Abilities Screening Instrument (CASI) and/or a decline of 7 points at any CASI level, to estimate age and sex-specific incidence rates. Patients scoring below the cut scores will have routine, standardized neurologic and neuropsychological evaluations. The followup of the cohort to the year 2001 will yield approximately 127 new cases of dementia. Risk factors for dementia subtypes will be examined in this group, including possible protective factors which show preliminary associations with cognitive impairment and prevalent disease, such as estrogen therapy replacement, head circumference and the apolipoprotein E-e2 (apoE) allele. Changes over time in CASI scores in the cognitively intact cohort also will be analyzed with regard to apoE genotype and other host factors. Finally, standardization efforts between the study sites will focus on the enhancement of the uniformity of diagnostic methods, and cross-site data analysis to compare rates and risk factors.